2-Acetylacteoside improves recovery after ischemic stroke by promoting neurogenesis via the PI3K/Akt pathway

  • Free Radic Biol Med. 2024 Nov 20:225:415-429. doi: 10.1016/j.freeradbiomed.2024.10.268.
Meng Wang  1 ,  Songyu Xing  1 ,  Yang Liu  2 ,  Zongren An  2 ,  Xu Liu  3 ,  Tao Liu  4 ,  Han Zhang  4 ,  Yifan Dai  5 ,  Haiyuan Yang  6 ,  Yu Wang  7 ,  Ying Wang  8
Affiliations
  • 1. Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China.
  • 2. ICU, Nanjing Gaochun People's Hospital, 53 Maoshan Road, Gaochun District, Nanjing, 211300, China.
  • 3. Qilu Medical University, Shandong, 255300, China.
  • 4. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 5. Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China.
  • 6. Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
  • 7. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
  • 8. Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
PMID: 39396583 DOI: 10.1016/j.freeradbiomed.2024.10.268
Abstract

Ischemic stroke induces adult neurogenesis in the subventricular zone (SVZ), even in elderly patients. Harnessing of this neuroregenerative response presents the therapeutic potential for post-stroke recovery. We found that phenylethanoid glycosides (PhGs) derived from Cistanche deserticola aid neural repair after stroke by promoting neurogenesis. Among these, 2-acetylacteoside had the most potent on the proliferation of neural stem cells (NSCs) in vitro. Furthermore, 2-acetylacteoside was shown to alleviate neural dysfunction by increase neurogenesis both in vivo and in vitro. RNA-sequencing analysis highlighted differentially expressed genes within the PI3K/Akt signaling pathway. The candidate target Akt was validated as being regulated by 2-acetylacteoside, which, in turn, enhanced the proliferation and differentiation of cultured NSCs after oxygen-glucose deprivation/reoxygenation (OGD/R), as evidenced by Western blot analysis. Subsequent analysis using cultured NSCs from adult subventricular zones (SVZ) confirmed that 2-acetylacteoside enhanced the expression of phosphorylated Akt (p-Akt), and its effect on NSC neurogenesis was shown to be dependent on the PI3K/Akt pathway. In summary, our findings elucidate for the first time the role of 2-acetylacteoside in enhancing neurological recovery, primarily by promoting neurogenesis via Akt activation following ischemic brain injury, which offers a novel strategy for long-term cerebrological recovery in ischemic stroke.

Keywords
2-Acetylacteoside; Akt; Cerebrological recovery; Ischemic stroke; NSCs; Neurogenesis.
Products